The technology of active matrix flat-panel imagers (AMFPIs) has undergone extensive research and development for many x-ray imaging applications since its initial conception in the 1980s. As a result, electronic portal imaging devices (EPIDs) based on AMFPI technology have been extensively introduced to external beam radiotherapy environments. Megavoltage AMFPIs represent a highly compact, large area (up to -41x41 cm2), solid-state technology that can be used for radiographic, fluoroscopic and tomographic imaging. In radiographic mode, image quality is substantially improved compared to that of the previous "gold standard", standard port film. However, present AMFPIs make use of only -2% of the incident radiation, the result is that their detective quantum efficiency (DQE - a widely accepted observer independent measure of imager performance), although equivalent to or higher than that of other commercial portal imaging technologies, is still only -1%. Thus, significant improvements in DQE and image quality are possible. Consequently, the hypothesis to be examined in the proposed research is: "Through the incorporation of innovative strategies, the DQE of megavoltage AMFPIs can be substantially increased through more efficient use of the incident radiation." Two approaches for increasing DQE (by factors ranging from ~6 to 50) involving photoconductor and segmented crystalline scintillator technologies will be investigated, each of which offers the potential of significantly increasing x-ray detection efficiency while limiting both the spatial spread of secondary quanta as well as the generation of noise in those quanta. Ultimately, the clinical introduction of AMFPIs offering such significantly enhanced DQE would reduce the dose required for projection images to low, potentially negligible levels, provide soft-tissue contrast in tomographic images at clinically-practical doses, and possibly provide soft-tissue contrast in projection images at clinically-practical doses, thereby greatly assisting in the difficult task of treatment verification.